Mitochondrial Translation Efficiency Controls Cytoplasmic Protein Homeostasis

Publication date: Available online 10 May 2018
Source:Cell Metabolism
Author(s): Tamara Suhm, Jayasankar Mohanakrishnan Kaimal, Hannah Dawitz, Carlotta Peselj, Anna E. Masser, Sarah Hanzén, Matevž Ambrožič, Agata Smialowska, Markus L. Björck, Peter Brzezinski, Thomas Nyström, Sabrina Büttner, Claes Andréasson, Martin Ott
Cellular proteostasis is maintained via the coordinated synthesis, maintenance, and breakdown of proteins in the cytosol and organelles. While biogenesis of the mitochondrial membrane complexes that execute oxidative phosphorylation depends on cytoplasmic translation, it is unknown how translation within mitochondria impacts cytoplasmic proteostasis and nuclear gene expression. Here we have analyzed the effects of mutations in the highly conserved accuracy center of the yeast mitoribosome. Decreased accuracy of mitochondrial translation shortened chronological lifespan, impaired management of cytosolic protein aggregates, and elicited a general transcriptional stress response. In striking contrast, increased accuracy extended lifespan, improved cytosolic aggregate clearance, and suppressed a normally stress-induced, Msn2/4-dependent interorganellar proteostasis transcription program (IPTP) that regulates genes important for mitochondrial proteostasis. Collectively, the data demonstrate that cytosolic protein homeostasis and nuclear stress signaling are controlled by mitochondrial translation efficiency in an inter-connected organelle quality control network that determines cellular lifespan.

Graphical abstract

Teaser

Suhm et al. show that mitochondrial protein translation impacts cytoplasmic proteostasis and nuclear gene expression. By analyzing mutations in the highly conserved mitochondrial ribosome, they show that mitochondrial translation accuracy is linked to cytoplasmic proteostasis, ROS, and a novel interorganellar proteostasis transcription program (IPTP), impacting chronological lifespan.


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